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Lost memories could be restored by 'rewiring' brain

Lost memories could be restored by 'rewiring' brain
18:00 29 April 2007
NewScientist.com news service
Zoe Smeaton

It may be possible to restore lost memories with drugs that trigger the natural "rewiring" of brain cells, a new study in mice suggests.

The findings could lead to new treatments for neurodegenerative diseases in humans associated with impaired learning and memory loss, such as dementia, the researchers say.

Li-Huei Tsai at MIT in Cambridge, Massachusetts, US, and colleagues used mice that were genetically modified to produce a protein (p25) when fed an antibiotic. Previous studies have suggested that p25 is linked to brain cell death.

Before triggering p25 production, the mice were placed in a tank of water and trained to find their way to a platform submerged just below the surface. After the mice had developed a long-term memory of the task, the team induced p25 in the rodents, which led to loss of neurons, learning ability and memory.

To see if these faculties could be restored, the mice were placed in an environment enriched with toys and wheels. When the stimulated mice were retested, the researchers found they did better at the memory task than before.

Not gone but forgotten
"If memories can be recovered then that suggests they were never erased and indicates that perceived memory loss is likely to be due to an inability to retrieve memories," Tsai says.

The mice from the enriched environment turned out to have higher levels of "synaptic marker proteins", an indication that the "wiring" between neurons in the brain had been re-established.

Long-term gain
The next step then was to see if drug-induced histone-tail acetylations could help recover long-term memory. Tsai's team targeted enzymes called HDACs, which prevent acetylation of histones. The researchers took mice that had lost long-term memory and injected them with a drug that inhibited HDACs. When tested, the team found that these mice were better able to find the platform in the water.

Tsai thinks that HDAC inhibitors seem to initiate rewiring of neurons. "If we could use drugs to facilitate that process I believe it would be very beneficial to people suffering from advanced stages of neurodegeneration," she says.

Karl Giese, who studies learning and memory at Kings College London in the UK agrees that the study could have therapeutic value. "Before this we didn't really have a handle on what we needed to do to treat dementia, so to have identified HDAC inhibitors as a drug target is very important," he says.